A survey of pharmacists' perception of the work environment and patient safety in community pharmacies during the COVID-19 pandemic.

Background: Community pharmacies have changed during the COVID-19 pandemic, and new routines have been introduced to address the needs of customers and staff and to reduce the risk of spreading infection. Burnout has been described among staff possibly due to a changed working climate. However, little research has focused on the pandemic's effect on patient safety in community pharmacies. Objective: To examine pharmacists' perceptions of the impact of the COVID-19 pandemic on workload, working environment, and patient safety in community pharmacies. Methods: A survey was distributed to all Swedish community pharmacists, constituting a census study. Questions regarding the pharmacists' perception of the impact of the pandemic on workload, working environment, and patient safety were included. Respondents were asked to provide comments on their working situation. Quantitative results were analysed using descriptive statistics, and comments were analysed using qualitative content analysis. Results: The response rate was 41% (2034 responses). Most pharmacists (62%) considered the workload to be increased during the pandemic while work environment deteriorated (physical work environment was considered worse by 47% of respondents while psychosocial work environment was considered worse by 59%). Despite this, many respondents (55%) believed that patient safety was not affected. Neither having had COVID-19 nor being afraid of contracting it, influenced these perceptions in any substantial way. Findings were consistent regardless of education, professional role, number of years in community pharmacies, or special assignments in the pharmacies. According to the respondents, the communication within pharmacy companies during the pandemic was inadequate. Conclusions: The impact of the pandemic on working conditions is in line with previous findings but the effect on patient safety needs further studies. The respondents felt the management had a limited understanding of the conditions during the pandemic, which stresses the importance of good and clear communication during a crisis.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size.

The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development. YAP function has been extensively characterized in epithelial cells and tissues, but its function in adult skeletal muscle remains poorly defined. Here we show that YAP positively regulates basal skeletal muscle mass and protein synthesis. Mechanistically, we show that YAP regulates muscle mass via interaction with TEAD transcription factors. Furthermore, YAP abundance and activity in muscles is increased following injury or degeneration of motor nerves, as a process to mitigate neurogenic muscle atrophy. Our findings highlight an essential role for YAP as a positive regulator of skeletal muscle size. Further investigation of interventions that promote YAP activity in skeletal muscle might aid the development of therapeutics to combat muscle wasting and neuromuscular disorders.

11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism.

PURPOSE: To evaluate whether dexamethasone suppression treatment can improve (11) C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA). MATERIALS AND METHODS: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small "hot-spot" regions of interest comprising 4 pixels (SUVhs) and 1 pixel (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded. RESULTS: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to nonfunctional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p < 0.05), but tumour SUV was not significantly decreased after suppression in either PA or nonfunctional tumours (p > 0.05). However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p > 0.05). CONCLUSION: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series, dexamethasone-suppressed MTO-PET was unable to increase the tumour-to-normal adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.

Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism.

PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.

Outcome after endovascular revascularization of atherosclerotic renal artery stenosis.

BACKGROUND: With an aging population, more patients might be treated for atherosclerotic renal artery stenosis (ARAS). The goal of this treatment is to achieve a dialysis-free life or a well-controlled blood pressure with reduced risks of cardiovascular complications. PURPOSE: To analyze the clinical outcome of percutaneous transluminal renal artery angioplasty without stenting (PTRA) or with stenting (PTRS) for ARAS at one center. MATERIAL AND METHODS: The study group comprised 152 patients who underwent 203 PTRA/PTRS. All had hypertension, and 45% had azotemia. A retrospective collection of baseline and postprocedural number of antihypertensive drugs, blood pressure, and serum creatinine were analyzed during a follow-up of 3-18 months. RESULTS: Technical success rate was 95%, and clinical benefit was seen in 63% of patients. Complications included a 30-day mortality rate of 1.5%, a total complication rate of 35%, and major adverse events in 13%. The major adverse events were highly related to azotemia. Major adverse events within 30 days, with permanent disability, were seen in 5% and almost exclusively in patients with moderate or severe renal impairment. A subgroup analysis of 28 patients with renal duplex resistive index (RI) pre-PTRA/S and 6 months' follow-up showed a benefit of PTRA/PTRS in 17 (68%) of the 25 patients with RI <80 and in all three (100%) of the patients with RI >or=80. CONCLUSION: Endovascular treatment of ARAS has an excellent technical success rate, with a clinical improvement rate of >60%. However, it is associated with a considerable complication rate. Serious complications are seen mainly in azotemic patients. Predictors of clinical response could not be identified. Renal duplex RI is questioned as a predictor of clinical outcome.

A prospective comparison of duplex ultrasonography, captopril renography, MRA, and CTA in assessing renal artery stenosis.

PURPOSE: To prospectively compare the diagnostic accuracy of duplex ultrasonography, captopril renography, computed tomography angiography (CTA), and 3D Gd magnetic resonance angiography (MRA) in diagnosing hemodynamically significant renal artery stenosis (RAS). MATERIAL AND METHODS: The standard of reference was measurement of transstenotic pressure gradient. Fifty-eight hypertensive patients with suspicion of RAS were evaluated, when possible, by all five techniques. Sensitivity and specificity to detect RAS were compared for each technique on both a patient and kidney basis. Discrepancies were evaluated separately and classified as borderline, method dependent, or operator dependent. RESULTS: The prevalence of RAS was 77%. The sensitivity/specificity of ultrasonography, captopril renography, CTA, and MRA in detecting kidneys with RAS was 73/71%, 52/63%, 94/62%, and 93/91%, respectively. Ultrasonography had a significantly lower sensitivity than CTA and MRA (P<0.001) but higher than captopril renography (P = 0.013). Borderline RAS was the main cause for discrepancies. CONCLUSION: MRA and CTA were significantly better than duplex ultrasonography and captopril renography in detecting hemodynamically significant RAS. The ultrasonography criteria for RAS based on the evaluation of renal peak systolic velocity and renal/aortic ratio are questionable. Captopril renography cannot be recommended for assessing RAS.

Prevalence of sleep apnoea and snoring in hypertensive men: a population based study.

BACKGROUND: Several studies have reported an association between sleep disordered breathing (SDB) and hypertension (HT) but there is still a debate as to whether this is an effect of confounders. Some researchers have found an age dependent relationship between SDB and HT with higher risk at lower ages. A case-control study was performed in hypertensive men and non-hypertensive male controls matched for age and body mass index to assess whether there is an independent association between SDB and HT. If so, we further wanted to investigate whether this effect is age dependent. METHODS: An overnight sleep study was performed in a population based, age stratified sample of 102 hypertensive men aged 43-82 years and 102 non-hypertensive controls. RESULTS: Hypertensive subjects had a significantly higher prevalence of SDB than non-hypertensive subjects (apnoea-hypopnoea index (AHI): 10.8 v 7.3; desaturation index (DI): 8.5 v 5.2; AHI >or=10: 37% v 24%, p<0.05; DI >or=10: 29% v 12%; lowest desaturation: mean (SD) 81.9 (7.3) v 84.7 (6.1), p<0.01). After adjusting for neck circumference and physical inactivity, DI >or=10 and lowest desaturation were still independent predictors of HT with adjusted odds ratios of 2.3 (95% CI 1.0 to 5.3) and 0.94 (95% CI 0.89 to 0.99), respectively. When the subjects were split into two groups according to age (<60 and >or=60 years), the influence of DI >or=10 on HT was strongest in the younger men (adjusted OR 4.3 (95% CI 1.0 to 19.3 v 2.1 (95% CI 0.7 to 6.5)) and the association between minimum oxygen saturation (SaO(2)) and HT reached statistical significance in the younger men only. CONCLUSION: SDB is more prevalent in men with HT than in controls. DI >or=10 and lowest desaturation are independent predictors of HT irrespective of confounders. The results indicate that the influence of SDB on HT is more pronounced in younger and middle aged men than in those above 60 years.

Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients.

OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Treatment with irbesartan or atenolol improves endothelial function in essential hypertension.

OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.

Regression of left ventricular hypertrophy in human hypertension with irbesartan.

BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

Eating behavior in Prader-Willi syndrome, normal weight, and obese control groups.

OBJECTIVE: Hyperphagia in Prader-Willi syndrome (PWS) is hypothesized to be due to hypothalamic dysfunction; thus the study of individuals with PWS might illustrate how hypothalamic dysfunction affects eating behavior. The aim of this study was to document the microstructure of the eating behavior in patients with PWS and to compare it with that of members of obese and normal weight control groups of the same age. STUDY DESIGN: Nine subjects with PWS (age, 10 +/- 4 years), 20 normal weight subjects (age, 12 +/- 3 years), and 20 obese subjects (age, 12 +/- 4 years) were served an excess lunch meal (hash) on a hidden scale built into a table and connected to a computer. The plate of food is placed on top of the scale, and when the food is eaten, the change in food weight is registered continuously. An eating curve is displayed online. After the meal, the eating data are fitted to a polynomial, and the computer calculates the amount of food eaten, time of consumption, eating rate (initial and total), and rate of deceleration. RESULTS: Subjects with PWS were found to have a longer duration of eating (P =.04) and a slower initial eating rate (P =. 01) compared with members of both obese and normal weight groups. In subjects with PWS, 56% of the eating curves were non-decelerating (linear or accelerating) compared with 10% of the normal weight group and 30% of the obese group (P =.02). CONCLUSION: The microstructure of the eating behavior in subjects with PWS differs from that of members of obese and normal weight control groups. Thus the eating behavior found in subjects with PWS might be due to decreased satiation rather than increased hunger.

Left ventricular hypertrophy is associated with an attenuated endothelium-dependent vasodilation in hypertensive men.

To investigate the relationship between left ventricular hypertrophy (LVH) and endothelium-dependent vasodilation (EDV), 30 untreated hypertensive patients, 18 treated hypertensives (53 +/- 7 years, all males) and 26 age-and sex-matched healthy normotensive controls, underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). Forearm blood flow was measured by venous occlusion plethysmography and LVH was measured by echocardiography. The reduction in forearm vascular resistance during MCh infusion (4 microg/min) was significantly smaller in the hypertensive patients with LVH when compared to those without LVH, both in the untreated (-61 +/- 12%, n = 19 vs -72 +/- 4%, n = 11, p < 0.01) and in the treated group (-60 +/- 15%, n = 11 vs -75 +/- 5%, n = 7, p < 0.01). Thereby, EDV was significantly impaired only in the hypertensive patients with LVH when compared to controls (-77 +/- 7% at MCh 4 microg/min, p < 0.001). EIDV was not significantly different between patients with and without LVH and controls. In conclusion, the presence of LVH was related to endothelial dysfunction, both in untreated and treated hypertensive patients, suggesting either a role for endothelial function in the development of LVH, or that a dysfunctional endothelium and LVH are coexisting markers of a more severe hypertensive disease.

Endothelium-dependent vasodilatation in treated and untreated hypertensive subjects.

It has repeatedly been shown that endothelium-dependent vasodilatation (EDV) is impaired in patients with untreated hypertension. The effect of antihypertensive treatment on EDV has, however, not been extensively investigated. In the present study, EDV and endothelium-independent vasodilatation (EIDV) were studied in 20 untreated and 41 treated hypertensive subjects and in 26 matched, normotensive controls by means of infusion of methacholine (MCh), 2 and 4 microg/min, evaluating EDV, and nitroprusside (SNP), 5 and 10 microg/min, evaluating EIDV, in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The vasodilatory action of MCh was impaired in untreated hypertensives compared with controls, with the response in the treated hypertensives in between the other two groups (p < 0.01 vs both of the other groups). EIDV, on the other hand, was enhanced in the treated hypertensives (p < 0.01), so that the MCh to SNP FBF ratio, an index of endothelial function, was attenuated in both treated and untreated hypertensives (0.97 +/- 0.24 and 0.96 +/- 0.15, respectively), compared with controls (1.27 +/- 0.29, p < 0.001). Both EDV and EIDV declined with increasing number of antihypertensive drugs used in the treated hypertensives (p < 0.05). In conclusion, the endothelial function index was found to be similarly depressed in both treated and untreated hypertensive subjects compared with normotensive controls. Antihypertensive therapy seems to improve the vasodilatory capacity in general rather than enhancing endothelial function.

Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.

Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.

Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm.

UNLABELLED: Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstrictor endothelin in this model has not been investigated. METHODS: Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir-ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A similar correlation coefficient (r=-0.69) was found in healthy subjects. CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.

Local vasodilatation with metacholine, but not with nitroprusside, increases forearm glucose uptake.

Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.

Captopril, but not nifedipine, improves endothelium-dependent vasodilation in hypertensive patients.

The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.

Effects of milk or water on lunch intake in preschool children.

In Sweden, milk and milk products are important sources of daily energy intake but the role of milk with preschool lunch meals has been debated frequently and water is often alternatively given today. We studied the effects of milk or water on lunch energy intake. Water or milk alternatively was served in a controlled, within-subject design on 12 occasions to 36 children aged 4-6 years, and energy intake was analysed at an individual level in three typical preschool lunches with a varying degree of preference among the children. When milk was given with the meals, a mean additional energy intake of 17% (p<0.0001) was found. The pattern was similar among boys and girls and irrespective of the lunch dish served. However, for the least preferred dish (fish with potatoes) milk helped to increase the energy intake by 26%. Physical activity measured as MET units (energy expenditure/body weight), atmosphere at the table as registered by a three-graded scale, and meal duration did not differ with meals or milk/water. Milk with preschool lunch meals seems to be a significant source of energy to achieve nutritional goals for this group of children.

Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns.

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.